In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 5004-5004
Abstract:
IQGAP2 is a member of three IQGAP scaffolding proteins and involved in cytoskeletal reorganization and adhesion of cells. It has been described as a putative tumor suppressor affecting tumor development and progression. Our aim in this study was to analyze the role of IQGAP2 in colorectal cancer (CRC). By means of microarray analyses we previously found IQGAP2 expression to be downregulated in CRC and suppressed by Maspin. Here we measured IQGAP2 expression by RT-qPCR in 17 MSI-H (high microsatellite instability) and 19 MSS (microsatellite stable) CRCs as well as in three MSI and three MSS CRC cell lines, respectively. Furthermore, we analyzed the methylation status of the IQGAP2 promoter and studied the subcellular localization of the IQGAP2 protein. Using an in vitro system for overexpressing and silencing IQGAP2 we investigated the effect of IQGAP2 on cellular migration applying Real-Time Cell Analyzer (RTCA) technology. Stably overexpressing Maspin transfected CRC cell line SW480 showed IQGAP2 loss on mRNA and protein level. IQGAP2 expression was reduced in 86% (30/36) of tumors compared to normal tissue (p & lt;0.001) and lower in MSS tumors compared to MSI tumors (p=0.039). Consistently, IQGAP2 mRNA levels were also downregulated in CRC cell lines. None of the cell lines, tumor or normal tissue samples analyzed showed IQGAP2 promoter methylation. Immunofluorescence analysis of CRC cells revealed IQGAP2 distribution in plasma membranes and more intensely in areas of cell-cell contacts. Migration assays showed increased cellular migration after IQGAP2 knockdown and impaired migration after overexpression of IQGAP2. We provide evidence that IQGAP2 expression is regulated by Maspin and may have an important effect on cellular migration in colorectal cancer. Citation Format: Benedikt Gröschl, Marcus Bettstetter, Tamara Widmann, Ferdinand Hofstädter, Wolfgang Dietmaier. Iqgap2 is downregulated in colorectal cancer (crc) and involved in cellular migration. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5004. doi:10.1158/1538-7445.AM2014-5004
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-5004
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
